HeLa cells chronically infected with either coxsackievirus B3 or B5 were shown to acquire a specific resistance to superinfection by only those viruses belonging to coxsackievirus group B. This resistance was found to result from altered cell surfaces, since superinfecting group B viruses did not attach or eclipse normally. These findings have served as a basis for continuation of studies of the early interaction of enteroviruses with host cells. Emphasis is directed toward the development of methods to study the specific viral receptors of the cell surface and of isolated plasma membranes. By use of radioisotope techniques, density gradient centrifugation, chromatographic separation, polyacrylamide gel electrophoresis and immunochemical procedures, plans are presented to characterize coxsackieviruses following elution from HeLa cells. Attempts will be made to solubilize enterovirus proteins in order to define the function of each protein. Efforts will be continued to find means to inhibit virus elution and to enhance the uncoating of enteroviruses so that the fate of viral proteins and nucleic acid may be followed during initiation of productive infection. Plans are made to extract and characterize enterovirus receptors from cells, cell membranes and from eluted virus. Evidence for a sub-group specificity of receptors for enteroviruses will be sought. Plans are made to determine the relationship between coxsackievirus receptor formation and stages in the differentiation of myogenic cells in culture. It is anticipated that the results of these studies will be useful in defining the cell surface events leading to productive virus infection and in providing a rational basis for the development of specific inhibitors to infection by enteroviruses.